Customized high resolution CGH-array for clinical diagnosis reveals additional genomic imbalances in previous well-defined pathological samples

Authors

  • Elena Vallespín,

    1. Section of Functional and Structural Genomics of Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain
    2. CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain
    Search for more papers by this author
  • María Palomares Bralo,

    1. Section of Functional and Structural Genomics of Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain
    2. CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain
    Search for more papers by this author
  • M. Ángeles Mori,

    1. CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain
    2. Section of Cytogenetics of Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain
    Search for more papers by this author
  • Rubén Martín,

    1. Section of Functional and Structural Genomics of Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain
    2. CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain
    Search for more papers by this author
  • Sixto García-Miñaúr,

    1. CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain
    2. Section of Clinical Genetics of Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain
    Search for more papers by this author
  • Luis Fernández,

    1. Section of Functional and Structural Genomics of Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain
    2. CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain
    Search for more papers by this author
  • M. Luisa de Torres,

    1. CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain
    2. Section of Cytogenetics of Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain
    Search for more papers by this author
  • Fe García-Santiago,

    1. CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain
    2. Section of Cytogenetics of Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain
    Search for more papers by this author
  • Elena Mansilla,

    1. CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain
    2. Section of Cytogenetics of Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain
    Search for more papers by this author
  • Fernando Santos,

    1. CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain
    2. Section of Clinical Genetics of Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain
    Search for more papers by this author
  • Victoria E. M-Montaño,

    1. Section of Functional and Structural Genomics of Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain
    Search for more papers by this author
  • M. Carmen Crespo,

    1. Section of Functional and Structural Genomics of Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain
    Search for more papers by this author
  • Sol Martín,

    1. Section of Functional and Structural Genomics of Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain
    Search for more papers by this author
  • Victor Martínez-Glez,

    1. Section of Functional and Structural Genomics of Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain
    2. CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain
    Search for more papers by this author
  • Alicia Delicado,

    1. CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain
    2. Section of Cytogenetics of Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain
    Search for more papers by this author
  • Pablo Lapunzina,

    1. CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain
    2. Section of Clinical Genetics of Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain
    Search for more papers by this author
  • Julián Nevado

    Corresponding author
    1. CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain
    • Section of Functional and Structural Genomics of Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain
    Search for more papers by this author

  • Conflict of interest: none.

Correspondence to:

Julián Nevado, Ph.D., MBA, INGEMM—Instituto de Genética Médica y Molecular Hospital, Universitario La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain.

E-mail: jnevado@salud.madrid.org

Abstract

High-resolution array comparative genomic hybridization (aCGH) is a powerful molecular cytogenetic tool that is being adopted for diagnostic evaluation of genomic imbalances and study disease mechanisms and pathogenesis. We report on the design and use, of a custom whole-genome oligonucleotide-based array (called KaryoArray®v3.0; Agilent-based 8 × 60 K) for diagnostic setting, which was able to detect new and unexpected rearrangements in 11/63 (∼17.5%) of previous known pathological cases associated with known genetic disorders, and in the second step it identified at least one causal genomic imbalance responsible of the phenotype in ∼20% of patients with psychomotor development delay and/or intellectual disability. To validate the array, first; we blindly tested 120 samples; 63 genomic imbalances that had previously been detected by karyotyping, FISH and/or MLPA, and 57 sex-matched control samples from healthy individuals; secondly a prospective study of 540 patients with intellectual disabilities, autism spectrum disorder and multiple congenital anomalies were evaluated to confirm the utility of the tool. These data indicate that implementation of array technologies as the first-tier test may reveal that additional genomic imbalances could co-exist in patients with trisomies and classical del/dup syndromes, suggesting that aCGH may also be indicated in these individuals, at least when phenotype does not match completely with genotype. © 2013 Wiley Periodicals, Inc.

Ancillary